What is the main reason why cruise flight in the transition layer is prohibited?
The main reason for the transition layer is to assure separation between the highest usable altitude (TA) and the lowest usable FL (TRL). That means it has to be at least 1000ft thick.
If the QNH is 1014 or above the transition level is always just 1000ft above the TA (5000ft and FL60) because the whole FL system is shifting upwards above the MSL. This means for each hPa above standard QNH 1013 your transition layer will be about 30ft thicker.

If QNH drops to 1013 or below the opposite happens: The base of the FL system falls below MSL, so FL000 is at -30ft MSL per 1hPa below 1013.

If QNH is 1003, the difference between 5000ft and FL60 is only 700ft because 1000ft-(10hPa*30ft)=700ft. In this case the TRL above TA 5000ft has to be FL70 to assure the separation between highest altitude and lowest FL is at least 1000ft.
So now we have a transition layer with one spare FL - FL60. If one would now fly at 6000ft we only have the above mentioned 700ft to FL70; if one would fly at FL60 only 700ft to 5000ft. This is why the transition layer may not be used for cruise flight