Aight, Imma make you sit in a Lazy Boy chair all day, non-stop. You can't shift around, ya can't put your legs up and down, nothing, sit still.
Now, you can do that, or you can sit on a wooden barstool, but you can shift as you please, get up, stretch your legs, whatever you want, all day.
Which is more comfortable under the circumstances?
The main thing about 'non upright' bike designs is that you're meant to, as in, they're a 'legitimate'/built into the bike, use a varied amount of hand and body positions. You're never stressing anything.
You can change your hands on a flat bar bike, or an upright bike, but it wasn't designed for that and you're either losing effectiveness or safety or both.
After riding a road bike before awhile, I had to ride a buddy's Walmart special back somewhere for him, and being in the headwind on that was fucking infuriating, knowing I could really only duck a bit more and be mad.