If you can see outside when looking down those holes, you should be concerned about keeping "critters" out.
I have used steel wool on the BIG holes in the floor of our rig, (and all the RVs have them) then sprayed in the expanding foam. Little holes all got the foam. I made sure the membrane on the bottom was closed up tight with no openings, and then I foamed all the holes in the frame that didn't have a purpose.
2008 Cruiser CF26RK
2013 Ford Eco-Boost
Heavy duty payload - Max tow