There are a relatively small number of people who get to fly 350-ton airplanes in their career. The number of people who train on those airplanes is smaller. An even smaller number of those trainers get to train on 350-ton airplanes at a number of airlines around the planet.
That last group can tell you a few stories (if they are willing to be candid) that would reveal that quite often you have 300 innocent passengers who are entrusting their lives to flightdeck occupants who are utterly bereft of any skill, awareness or initiative, and are visibly uneasy and uncertain at every phase of flight.
A personal sim favorite is to clear two of these occupants for a visual approach. There will be a two minute flurry of FMC programming and then the approach will be flown from downwind all the way to the threshold without anyone ONCE looking out the window until they are forced to at 50' when the pitch bar commands level flight.
The threat goes way beyond any degradation in manual flying skills as these never existed in the first place - there are any number of active widebody pilots who are temperamentally unsuited to the chair.