In general IC engines are at their most fuel-efficient in the middle RPM range, but there's all sorts of other variables in play (like how well matched the engine and transmission characteristics are, and usage cycles in a particular application). But I'm not surprised that the 25% larger engine was overall more economical.
Many decades ago when I used to read car magazines regularly (before I was old enough to drive one!), some car models were available with a wide range of engine options e.g. the Ford Capri had options from 1.3L 4 cyl to a 3L V6, reviews often commented that a particular engine size was the 'sweet spot' of drivability versus fuel economy - the small engines had to be driven hard just to get around at a reasonable speed, whereas the big engines probably spent a lot of their time in less-efficient RPM ranges (and were heavier/had higher frictional losses/used more fuel when idling etc.).
Small point - turbocharged EMD 2-stroke diesel engines use a single, special, turbocharger that is mechanically driven in lower RPM/lower exhaust gas flow situations, with the mechanical drive automatically disconnecting (via an overrun clutch mechanism) when the exhaust gas flow is sufficient to drive the compressor from the exhaust turbine alone - from what I've read, that happens around notch 5 or 6. There is not a separate supercharger (blower). Non-turbocharged EMD 2-stroke engines use a mechanically driven Roots-type blower instead.
AFAIK, max hp at rail for a class 66 is around 2600-2700hp and 2300-2400hp in notch 7. According to this post -
https://www.railforums.co.uk/threads/class-93-tri-mode-loco.210779/post-7142500 - a 66 is most fuel-efficient in notch 6, a bit worse in notch 7 and much worse in notch 8.