The big issue is exhaust getting into the house. Duct leaks from the supply side cause the house to have a negative pressure, which can cause air to get pulled in from the garage. Exhaust entering the home can be dangerous and can lead to health issues.

The first step is to find what the maximum house depressurization would be with combinations of the airhandler on, closed bedroom doors, and any exhaust fans running. Do what you can to eliminate these pressures. Check to make sure there aren't any air intakes (returns) inside the garage.

To determine how leaky the garage to house connection is test the house leakage at 50 Pa, then pressurize the garage to 50 Pa; if you see any drop in flow, there's a connection between the two.

Next, depressurize the house and use a smoke puffer to test the garage to house connection. Seal everything between these two zones.