Can be quite a few things.
It's a new route and your route image is very low for me(solution : wait for it to grow naturally, or invest in route marketing for a few months for it to happen quicker)
Your plane is too small for a too long range(the the game issues a warning when you are planning the route - solution, fly a bigger fleet group)
You are having a tech stop(This is a killer, especially when it's combined with the too small penalty - solution, fly a bigger fleet group with better range)
You are taking off and landing at night(solution : schedule better your flights, and avoid night trips, or divide night ticket prices by two)