And about the foundation of this mitzvah of sanctity the Toras Kohanim has “‘be holy’ – be separate”. Nachmanides, in his commentary on the Torah, explains at length this notion of separation as it is stated in this mitzvah, that it is separation from excessive comfort and pleasure – even if they are actions that are not prohibited to us. In one illustrative statement, he writes that it is possible for a person to be disgusting with [what would otherwise be] the permission of the Torah, see his holy words there.

וביסוד מצוה זו של קדושה איתא בתורת כהנים: “‘קדושים תהיו’ – פרושים תהיו” ,והרמב״ן ז״ל בפירושו על התורה האריך לבאר ענין פרישות האמור במצוה זו שהוא להתרחק מן הנאות ותענוגים יתירים, אף על פי שהם מעשים שאינן אסורים לנו, ובציור מבליט אומר שאפשר לאדם להיות נבל ברשות התורה ועין שם בדבריו הקדושים

Rav Shimon Shkop defined qedushah in terms of commitment to the cause of providing good to others. So he has to address this medrash (Toras Kohanim, a/k/a the Sifra, which predates the mishnah) that appears to be defining the mitzvah of being holy as separation. In particular, the Ramban’s (much quoted) further explanation, that this is separation is from things which are permitted by the black-letter of the law, but are still disgusting or self-belittling behaviors.

Even if we find a way to say that both definitions boil down to the same thing, there is a fundamental difference in attitude between the formulations, one that would lead to differences in action:

The Sifra could be taken to mean that holiness inheres in withdrawal from the pleasures of this world, that it’s associated with austerity and asceticism.

Rav Shimon is drawing a picture of holiness that is in action, not in cloistered retreat. It is in elevating the lot of others, not an other-worldly lifestyle.

The rest of this section is dedicated to showing how his conclusion is actually the more correct understanding of the verse and medrash.