As much as £710 million a year will be lost to the economy in northern England through failure to expand Heathrow, a study for the airport claims.
Any refusal to approve a third runway would jeopardise the Northern Powerhouse by cutting off key domestic air links, according to the research.
Heathrow offers domestic routes to eight cities in the UK and has pledged to increase the number to at least 14 if wins permission to build a third runway.
A study by Frontier Economics warned that more airlines would be forced to fly directly to the north via continental European hubs such as Paris, Frankfurt, Amsterdam and Madrid without a third runway.
The government is expected to make a final decision on runway capacity in the south-east of England in the coming weeks.
Heathrow expansion was backed by the Airports Commission last summer but faces strong opposition.
Rival Gatwick claims that a second runway could be built faster and cost less.
Heathrow chief executive John Holland-Kaye, quoted by the Times, said: “Heathrow is the right choice for a long-term plan to back every corner of the UK.
“The government is going to struggle with the foundations of the Northern Powerhouse if a third runway isn’t built to support the region’s existing connectivity.
“To rebalance and strengthen the British economy, the UK needs a domestic hub airport that can compete with our unconstrained hub rivals abroad and that’s something only Heathrow can deliver."
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