External HD Changing the quality of the sound?


Hi everyone! It's my first thread i start in this community and i'm willing to go far in the journey of Hi-Fi audio :)
So i was wondering, is it real that if you put your audio file in an external hd it lower the quality on the outline?
I still don't have dac to test it so i wanted to be sure before putting my library in it, since my external hd is a 2tb and the one i have in my imac is a 500gb and is full...
Also, is it true that the type of connection used for my hd is changing the quality (usb 2.0, usb 3.0, firewire800)?
I know how it could affect it, i just want to know if it is all true?
freb03
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Spent time the last 2 evenings A/B 'ing CDP vs Apple Lossless version with BitPerfect through DAC. Listened mainly to Peter Gabriel's "So" that I am very familiar with...especially tracks 3, 6 & 9. Have to say I found it VERY hard to tell a difference. Any differences were subtle if not imagined but with CDP sounding a little more "there" (I did try to make sure SPLs were the same). I'll continue to experiment but at this point computer audio makes sense mainly for convenience. Can fit a lot of CDs on a portable 1TB hard drive. Also good for downloading music files that aren't available in physical format. To me, doesn't seem worth the hassle of "ripping" CDs to hard drive for a superior music listening experience. That's not to say others aren't enjoying something improved by doing so. Just that to me, given what I'm willing to invest $ & time-wise to realize an improvement in computer audio - not worth it right now.
I find that my EMM Labs XDS1 and Playback Designs still sound better with a spinning disc but the software keeps sounding better so I suspect it might overtake it eventually.