Maybe out in left field, but...
Could there be some "components" in the human body that are "sensitive" to travel in ways that could be similar to those found in other species, such as birds? Perhaps sensitive to changes in the magnetic field, sunlight angles along with the obvious pressure changes?
Parts of our body may "know" that we've traveled significant distances whilst sitting on our arse and pushing buttons. We are well aware of the lower humidity in most flightdecks, along with other well known factors.
Then again, just sitting at one's desk at home, in a restricted position, (without the relatively frequent up and downs for coffees, loos, snacks, etc, that happen in home settings) for 4 to 8 hours, could be just as fatiguing as a flight of equal length of time?