Pope Francis headed to the United States on Tuesday after urging Cubans to undertake a “revolution of tenderness’’ at a time of potential momentous changes as the nation opens to America after decades of Cold War-spawned hostility.

Shortly before 12:30 p.m., the pontiff’s chartered Alitalia jet left the runway in Santiago after farewell greetings from dignitaries including Cuban President Raúl Castro. The pope, who carried his own bag onto the flight, is expected to arrive at Joint Base Andrews outside Washington at 4 p.m.

Francis — speaking hours earlier at a site of important national unity in Cuba — steered clear of previous comments during the trip that indirectly, but clearly, jabbed at Cuba’s leaders to offer more room for civil and faith groups, and speed permission for new Catholic churches.

The pontiff, however, urged Cubans to look to themselves — not the state — to transform their lives and communities.

“We are asked to live the revolution of tenderness,” the pope said at a Mass at the Basilica of Our Lady of Charity of El Cobre, just outside Santiago, one of Cuba’s most sacred sites. Santiago, in eastern Cuba, also carries deep ideological symbolism as the birthplace of Fidel Castro’s revolution in the 1950s.

“Our revolution comes about through tenderness, through the joy which always becomes closeness and compassion, and leads us to get involved in, and to serve, the life of others,” the pope said in a theme that is likely to be repeated during his U.S. appearances.

The pontiff also praised past generations for keeping Catholic life alive during decades of official clampdowns.

“The soul of the Cuban people . . . was forged amid suffering and privation which could not suppress the faith,” he said. “Grandmothers, mothers, and so many others . . . kept open a tiny space, small as a mustard seed.”

The Lady of Charity is taken as a symbol of the nation, the mother of independence from Spain. She is cherished by believers and non-believers alike, and adored both by Cubans on the island and Cubans in exile.

“The Virgin of Charity unites us” is a popular phrase in the exile community and on the island, and in that sense the Mass will contain the essence of the hopes for rapprochement between the two nations that Pope Francis himself has promoted.

Pope Francis looks over Holguin, Cuba's fourth-largest city, on Monday. Francis is scheduled to head to the United States on Tuesday. (AP/AP)

Following the Mass, the pope traveled to Santiago in the popemobile, waving to throngs lining the streets. In the Cathedral of Santiago, he met with families and highlighted the theme of the pain of families that have been separated, a topic with heightened resonance in the context of divided Cuban families.

“Without family, without the warmth of home, life grows empty, there is a weakening of the networks which sustain us in adversity, nurture us in daily living and motivate us to build a better future,” he said.

“Societies which are divided, broken, separated or rigidly uniform are a result of the breakup of family bonds, the loss of those relationships which make us who we are, which teach us to be persons,” he added.

The pope also said that during his four days on the island, he had come to feel a part of the Cuban family: “Thank you, Cubans, for making me feel part of a family, for making me feel at home, in these days.”

The Archbishop of Santiago, Dionisio Garcia, described for Francis the challenges facing Cubans divided by emigration, economic pressures and a breakdown of family ties.

“Young people with families today want to have children but so often their plans turn into a problem, because so many young people have emigrated, or are separated for reasons of employment, or economic struggles, housing shortages,” he said, adding that Cuba’s low fertility rate and population decline “leaves our country to grow old” and “destabilizes families.”

“Our families want to be strengthened by your message of encouragement and hope,” Garcia said.

Before leaving Santiago, the pope blessed the city from an elevated terrace in front of the Cathedral, directly across historic Cespedes Park from the balcony where Castro proclaimed the victory of the revolution against U.S.-allied rulers.

“A people that takes care of its grandparents, its children and its poor has its triumph secured,” the pope said, as the audience filling the park cheered.

The pope’s next stop marks his first visit to the United States. Every program on the itinerary in both countries seemed steeped with history, starting with the pontiff’s flight.

It will surely be the first direct air link in generations from the eastern city of Santiago, birthplace of Fidel Castro’s revolution in the 1950s, directly to Joint Base Andrews in Maryland.

The pope’s first full day in the United States is to begin Wednesday with a ceremony on the South Lawn of the White House and a meeting with President Obama. Francis played a key role in opening talks that led to the historic restoration of diplomatic ties between Cuba and the United States.

On Thursday, Francis is scheduled to visit Congress and a homeless shelter in Washington, before flying to New York, where he will address the United Nations and visit the Ground Zero memorial. He is scheduled to celebrate Mass on Friday at Madison Square Garden.

Then he will fly to Philadelphia for a series of activities over two days, before returning to Rome Sunday evening.

Miroff reported from Havana. Brian Murphy in Washington contributed to this report.

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