There are theories about Howard being a spy, and that being the reason why the Luftwaffe targeted his flight over the Bay of Biscay, but they aren't really too convincing. There were other important people on the flight.
The most likely scenario is that the Luftwaffe pilots spotted the DC-3, identified it as an allied type, painted in standard RAF camouflage (despite bearing civilian registration markings) and decided to attack.
Oddly enough, there was another fatality in a DC-3 crash connected to the top billed cast of Gone with the Wind. In January 1942 the actress Carole Lombard who was the wife of Clark Gable (Rhett Butler) was returning to LA from a midwest War Bonds promotion tour when the plane on which she was travelling hit a mountainside in Nevada. The cause of the crash was simply a navigational error, but some theories were advanced that the plane had been sabotaged by Nazi agents.