The passes in the mountain ranges are high enough at roughly 7,000 feet (Donner Pass) and the Rocky Mountain passes at 8,000+ to cause some to experience fatigue more quickly than at sea level, but they are not high enough to cause altitude sickness. I've given many tours of Virginia City - up and down the mountainside at roughly 6,200 - and I found that flatlanders become winded more quickly than natives, but they all survived and a few minutes at a bar with a beer quickly resolved any issues. Granted, this is lower than some of the elevations on the historic trails, but they aren't high enough to cause more than modestly-premature exhaustion.