Southern demonstrated its depth when it scored three tries in the first 15 minutes to stamp its authority on the game at Watson Park.
Five players from the original squad are on Otago duty and no longer available for club games.
Southern scored five tries in the first half and had a commanding 35-5 lead at the break.
Southern was in complete control and added three more tries in the second spell.
It dominated the lineout through the efforts of blindside flanker Sam Crompton, locks Sam Gibson and Sam Gavegan.
Crompton and No 8 Andrew Stead were dominant in the loose. Stead was able to breach the advantage line from the scrums and mauls.
First five-eighth Julius Glasson directed play efficiently and his kicks to the corner kept the pressure on Harbour.
Centre Nick Jones, who has been promoted from the colts, showed speed and determination in scoring two tries.
The best players for Harbour were openside flanker Angus Duckett and Pete Mirrielees and Ben Nolan in the front row.
- Southern 52 (Nick Jones 2, Luke Herden, Andrew Stead, Sam Crompton, Sam Gavegan 2, Dave Ogilvie tries; Hamish Buick 6 con), Harbour 5 (Pete Mirrielees try). Halftime: Southern 35-5. Referee: Jeff Grubb.