Don't know about the manifold, but take a look at the PCV system. If the PCV valve is getting stuck wide open it could create a whistle trying to pull a ton of air through the vent side of the system.

If it has a MAF check the tube between the MAF and throttle body for splits (although I wouldn't think this would whistle), it would cause the gas mileage to go down as the computer tries to figure out what is going on.

 

Are you sure it's a motor whistle? My 03 F-150 has a drive train (transmission I think) whistle right at 50 mph just as you say. Doesn't do it at 49 or 51. (it probably does, but I can't hear it) Only happens when it's about 20 F or lower. It's been doing it since new. Doesn't hurt the gas mileage, though.