For planes specifically, acceleration, vibration (including turbulence), noise, lowered barometric pressure, variations of temperature and humidity. There are a bunch of different forces acting on your body essentially.
The physical effects that flight has on the body are very well documented due to the practice of in-flight medicine. In general, the results are a person being sleepy and hungry.
I did read somewhere that most commercial planes are only pressurised to mimic a fairly high altitude so if you’re used to living at sea level you might feel more exhausted because you’re not used to the lower-than-usual air pressure. That’s why you can feel particularly zapped after a flight even if you sleep.
A quick Wikipedia search tells me that a 767 is pressurised to 7000 ft which is significantly higher than Denver and SLC and just below Aspen.
Side note, my former company used to have us do driving training every month on the computer. We’ve watched so many videos that make the point of driving is work and physically/mentally exhausting. We have to follow all rules of the company even when driving company vehicle to and from work (I brought company vehicle home with me). So with that all being said, why don’t you pay us for drive time to and from the jobsite? You’re expecting me to follow your rules while even you say that it is “work”. They would also have us work a 12 hour shift then drive over an hour home. Your own driver training says that’s not ok. If you expect me to work 12 hours then my drive time should be part of that shift.
Pilot here. Moisture and quiet are your friends. Neither are plentiful in planes where the air is dry and the noise is constant. We use noise cancelling headsets and they make a huge difference. Investing in something like the Bose QC35 for consumers can be very smart. Also, drink a bunch of water before you get on the plane, and then drink more throughout the flight. And whatever you do, try to avoid alcohol. It dries you out.
EDIT: Pro tip: bring an empty water bottle with you through security and then fill it up from a water fountain near the gate.
Most of the top comments seem to miss the main answer:
Vibration and jostling for busses and cars, air pressure and some vibration for planes.
You’ll notice this on land if you go from an old or poorly designed car to one with a more comfortable ride. In the air, if you ride on Boeings Dreamliner, which uses better understanding of jet lag and fatigue to be less exhausting, you’ll see it there.
There are other factors, mentioned by others, such as noise, changing sights, unchanging positions, and more. But jostling and air pressure are the biggest.
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