Troubleshooting

My truck (Ford F250 heavy duty) starts shaking and loosing power after driving it for about an hour on the highway. The transmission has trouble shifting gears when this starts happening. This is new and started over the last 300 miles on a long drive. There is a small oil leak most people thing is a seal. I had the transmission fluid changed 500 miles ago. The check engine light is on--it was read as a couple of random misfires on cylinders 1 and 2. When this happens the gas mpg drops by about 50%.