It’s not clear to me that on balance highway driving is easier. The physics of a Semi going 65 mph are more relatively constrained. You can’t just solve all of your problems by slamming on the brakes like you almost can in city traffic. Even though the interstate is designed to mitigate this, the tails are probably just as bad, ie, pedestrian suddenly jumps out into the road. It doesn’t happen as often as it does in the city, but it does happen, and at 65mph pulling 80 tons, it’s a lot more demanding problem.

That said, a semi going through the night on the interstate can make some serious miles and is competitive with an airplane for a whole lot of what needs to be delivered.